From Pituitary Stem Cell Differentiation to Regenerative Medicine

The anterior pituitary gland is comprised of specialized cell-types that produce and secrete polypeptide hormones in response to hypothalamic input and feedback from target organs. These specialized cells arise during embryonic development, from stem cells that express SOX2 and the pituitary transcription factor PROP1, which is necessary to establish the stem cell pool and promote an epithelial to mesenchymal-like transition, releasing progenitors from the niche. Human and mouse embryonic stem cells can differentiate into all major hormone-producing cell types of the anterior lobe in a highly plastic and dynamic manner. More recently human induced pluripotent stem cells (iPSCs) emerged as a viable alternative due to their plasticity and high proliferative capacity. This mini-review gives an overview of the major advances that have been achieved to develop protocols to generate pituitary hormone-producing cell types from stem cells and how these mechanisms are regulated. We also discuss their application in pituitary diseases, such as pituitary hormone deficiencies.

In-silico Inhibitory Study of cFos-cJun Complex by T-5224 Based Small Molecule Analogs

Background:: Inflammatory diseases are one of the major concerns of today’s world, major disorders caused by inflammation includes, allergy, asthma, arthritis, hepatitis, autoimmune diseases, celiac disease etc. During most of these events, many protein and molecules expression were modulated and one such protein is AP-1 (c-Fos-c-Jun heterodimer complex). AP-1 is a dimeric protein activated by several physiological stimuli and environmental insults such as growth factors, polypeptide hormones, neurotransmitters, cytokines, cell-matrix interactions, UV irradiations, viral and bacterial infections. Objective:: Present study is mainly focus on designing of small molecule analogs to inhibit c-Fos-c-Jun complex, as the complex is involved in many inflammatory diseases and precisely involved in disease progression. Therefore, it had been considered as therapeutic target since more than a decade. Methods:: In the present study, an attempt was made to design the analogs of referral drug T-5224. 31 analogs of T-5224 were designed by chemoinformatics approach and subjected to ADMETox for screening. Results and Discussion:: Among the 16 compounds were found to pass the evaluation, all 16 compounds passed the toxicity evaluation except 7th molecule. The molecular docking study showed that the compounds 1, 2 and 16 were having high inhibition constant. Conclusion:: The preliminary results suggest the compounds 1, 2 and 16 are having the potential ligand binding capacity with cFos-cJun complex. Further analysis, with advanced tools, may results in potential small molecule to inhibit the c-Fosc- Jun complex.

Peptide Hormone Regulation of DNA Damage Responses

DNA damage response (DDR) and DNA repair pathways determine neoplastic cell transformation and therapeutic responses, as well as the aging process. Altered DDR functioning results in accumulation of unrepaired DNA damage, increased frequency of tumorigenic mutations, and premature aging. Recent evidence suggests that polypeptide hormones play a role in modulating DDR and DNA damage repair, while DNA damage accumulation may also affect hormonal status. We review the available reports elucidating involvement of insulin-like growth factor 1 (IGF1), growth hormone (GH), α-melanocyte stimulating hormone (αMSH), and gonadotropin-releasing hormone (GnRH)/gonadotropins in DDR and DNA repair as well as the current understanding of pathways enabling these actions. We discuss effects of DNA damage pathway mutations, including Fanconi anemia, on endocrine function and consider mechanisms underlying these phenotypes. (Endocrine Reviews 41: 1 – 19, 2020)

Classification of Neuroendocrine Tumors: Consensus Guidelines for the Management and Treatment

Neuroendocrine tumors (NETs) are neoplasms that arise from cells of the endocrine (hormonal) and nervous systems. Many are benign, while some are malignant. They most commonly occur in the intestine, where they are often called carcinoid tumors, but they are also found in the pancreas, lung and the rest of the body. Although there are many kinds of NETs, they are treated as a group of tissue because the cells of these neoplasms share common features, such as looking similar, having special secretory granules, and often producing biogenic amines and polypeptide hormones.